It is often necessary to determine the identity or internal structure of a compound and a common method used for this purpose is ion fragmentation. Tandem mass spectrometry (MS/MS or MS2) analysis, for example, is a common technique whereby target compound ions having a specific mass to charge ratio are first isolated and then fragmented. The resultant fragment ions are then mass analysed.
Quadrupole tandem mass spectrometers, which typically comprise two quadrupole mass filters (“QMF”) separated by a fragmentation cell, are prevalent and are commonly used for tandem mass spectrometry. The quadrupole mass filters are typically located within respective vacuum chambers and are operated at relatively low pressures as compared with the fragmentation cell.
Quadrupole mass filters are well known and typically comprise an analytical quadrupole in combination with a pre-filter quadrupole and a post-filter quadrupole. In operation, an RF voltage and a resolving DC voltage are simultaneously applied to the rod electrodes of the analytical quadrupole so that the mass filter operates in a mass or mass to charge ratio resolving mode of operation.
In certain situations tandem mass spectrometry (MS2) is either not sufficiently specific or else further structural information is required. If further structural information is required then an MS/MS/MS (or MS3) analysis may be performed whereby target compound ions are isolated and fragmented. Specific first generation fragment ions are then isolated and are further fragmented to form a plurality of second generation fragment ions. Successive repeats of isolation and fragmentation steps may be strung together and the general technique is commonly known as MSn.
Dedicated instruments capable of performing MS3 or MSn analysis are known. For example, U.S. Pat. No. 7,034,292 (Whitehouse) discloses arrangements comprising multiple multipole ion guides arranged in series, wherein collisional induced dissociation (“CID”) of ions is conducted by axially accelerating ions from one multipole ion guide into an adjacent multipole ion guide.
However, it is often desirable to be able to perform MS3 or MSn analysis in a less complex and more commonly available instrument such as quadrupole tandem mass spectrometer.
In order to perform MS3 and/or MSn analysis using a quadrupole tandem mass spectrometer it is necessary to use an existing part of the instrument to perform the one or more additional stages of mass isolation and fragmentation.
One known solution involves causing ions to fragment as they are transferred from one quadrupole mass filter into another quadrupole mass filter. For example, US 2003/0168589 (Hager) discloses an arrangement in which ions may be fragmented by accelerating them from one quadrupole rod set into another quadrupole rod set.
Another known solution is to use a quadrupole mass filter of a tandem mass spectrometer as a linear ion trap (“LIT”) and to perform multiple stages of isolation and/or fragmentation within the linear ion trap. Performing multiple stages of isolation and/or fragmentation within a single quadrupole mass filter provides more flexibility and control when compared with techniques in which ions are fragmented as they are transferred from one quadrupole mass filter into another quadrupole mass filter.
These techniques may also be used to perform fragmentation or MS2 analysis using a single quadrupole mass filter/linear ion trap.
Parent or precursor ions can be isolated within the linear ion trap using a variety of known methods.
There are various different known methods of fragmenting ions within a linear ion trap including: (i) resonant excitation wherein a “tickle” voltage is applied between diametrically opposite rods in order to radially excite an ion within the linear ion trap until the ion undergoes Collision Induced Dissociation (“CID”) via collision with a residual gas molecule; (ii) boundary activated dissociation comprising applying resolving RF/DC voltages to a linear ion trap to give the ions higher amplitude motion so as to cause Collision Induced Dissociation (“CID”) (see, for example, U.S. Pat. No. 6,015,972 (Hager)); and (iii) ion threshing wherein an axial DC field is applied along the length of a linear ion trap which is rapidly switched to drive the ions axially back and forth to cause Collision Induced Dissociation (“CID”) (see, for example, U.S. Pat. No. 5,847,386 (Thomson)).
The known boundary activated dissociation approach is relatively complex and requires tight control of the RF and resolving DC voltages applied to the quadrupole which can disadvantageously conflict with the other operational requirements of the quadrupole.
The known resonant excitation approach and the known ion threshing approach require various physical modifications to existing quadrupole mass filter or linear ion trap hardware which is disadvantageous.
US 2011/0309244 (Whitehouse) discloses a method in which collisional induced dissociation (“CID”) of ions is performed within a linear multipole ion guide by either: (i) exciting ions with a resonant frequency; (ii) releasing ions from the ion guide and then accelerating the ions back into the ion guide; or (iii) filling the ion guide with a critical level of ions. These approaches are again relatively complex and/or require various physical modifications to existing quadrupole mass filter or linear ion trap hardware which is disadvantageous.
It is therefore desired to provide an improved mass spectrometer.